Angiogenesis, the growth of new blood vessels, is important for organ development, wound healing and various pathological conditions such as tumor growth or proliferative retinopathies. Neovascularization depends on endothelial cell survival/proliferation, adhesive contacts of the endothelial cells with the extracellular matrix and with pericytes, on endothelial cell migration and sprouting, as well as on the function of growth factors. There is emerging evidence that inflammatory cells and components of the innate immunity regulate endothelial cell functions related to angiogenesis. 1) The complement system is a major component of the innate immunity. How complement may regulate angiogenesis is not clear. The participation of the complement system in hypoxia-driven retina angiogenesis and in tumor angiogenesis is currently under investigation by using complement components and inhibitors and genetically modified mice that lack the central complement component C3. In particular, we have found that complement is capable of regulating angiogenesis under pathologic conditions by regulating the polarization of macrophages to a pro-inflammatory macrophage phenotype 2) Hypoxia induces replication arrest in cells, nevertheless, in hypoxia-induced angiogenesis, such as during proliferative retinopathies, endothelial cells need to actively proliferate due to the presence of hypoxia-inducible factors. To understand this we studied the DNA repair response to hypoxia in endothelial cells, including the phosphorylation of histone H2AX. In vitro and in vivo studies revealed that H2AX and the DNA repair response due to hypoxia help endothelial cells overcome the hypoxia-induced replication arrest, thus allowing for maintenance of endotelial cell proliferation under hypoxic conditions and thereby promoting hypoxia-driven angiogenesis.